Case Presentation:

A 28–year–old African American male, recently diagnosed with HIV (CD4 count 12 cells/mm³) was admitted with a history of fever of 2 weeks duration. On exam, he had high grade fever of 38.5⁰ Celcius along with hepatomegaly. Laboratory studies showed pancytopenia with a hemoglobin of 6.9 g/dL with normal RBC indices, WBC count of 1800 cells/mm³ and platelet count of 29000/mm³. Hemolysis was ruled out by absence of schistocytes in the peripheral blood smear, reticulocyte count of 2.3% (normal 0.7–2.7%), and a haptoglobin level of 145 mg/dL (normal 41–165 mg/dL). Serum ferritin was >108000 ng/mL (normal 23–336 ng/mL), which was repeated twice to rule out lab error. His liver enzymes and LDH were normal at admission but over the next 5 days, steadily climbed to ALP 318 U/L, AST 431 U/L, ALT 82 U/L, with serum LDH level >5000 U/L. Despite adequate treatment of the primary HIV infection and prophylaxis for opportunistic infections, his clinical condition continued to deteriorate. Persistent pancytopenia provoked a bone marrow biopsy for further evaluation. Histopathology revealed numerous phagocytes engulfing budding yeasts of Histoplasma capsulatum compatible with a diagnosis of hemophagocytic lymphohistiocytosis. The diagnosis was supported by a strongly positive urine histoplasma antigen of >39 ng/mL. The patient was started on treatment with voriconazole for disseminated histoplasmosis. However he succumbed to his illness.

Discussion:

Hemophagocytic lymphohistiocytosis (HLS), first described in 1939, remains under diagnosed even today until autopsy specimens reveal it as the cause of death in several patients. HLS can either be primary with a genetic etiology or secondary to infection, malignancies or autoimmune disease. The catastrophic series of events that characterize this disorder are triggered by dysregulation in natural killer T–cell function. This results in cytokine overproduction, proliferation of macrophages which engulf red blood cells, white blood cells and platelets, hence the disease is also known as “macrophage activation syndrome”. There are no precise clinical guidelines for managing this rare disorder

Conclusions:

We report this case in order to increase awareness amongst hospitalists of this rare disorder. One should be familiar with the hallmarks of this disease, which include skin rash, hepatosplenomegaly and laboratory evidence of cytopenias, elevated liver enzymes, and high triglyceride and or ferritin levels. An early bone marrow biopsy can help confirm the diagnosis. Suspicion can lead to early recognition and treatment of the underlying cause, which apparently is the only treatment modality available for this potentially fatal disease.